Nuclear transport of protein TTC4 depends on the cell cycle.

TTC4 (tetratricopeptide repeat domain protein 4) is a putative tumor suppressor involved in the transformation of melanocytes. At present, the relationships between TTC4 and DNA replication proteins are largely unknown, as are the tissue distribution and subcellular localization of TTC4. Using reverse transcription with the polymerase chain reaction, we have observed that the murine TTC4 gene is ubiquitously expressed. Analysis of the TTC4 subcellular localization has shown that, upon overexpression, TTC4 localizes to the cytoplasm. Interestingly, co-expression with a known protein interaction partner, hampin/MSL1, results in the nuclear translocation of the TTC4 protein. The subcellular localization of endogenous TTC4 depends, however, on the cell cycle: it is mostly nuclear in the G1 and S phases and is evenly distributed between the nucleus and cytoplasm in G2. The nuclear transport of TTC4 is apparently a complex process dependent on interactions with other proteins during the progression of the cell cycle. Thus, the dynamic character of the nuclear accumulation of TTC4 might be a potential link with regard to its function in tumor suppression.